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NGƯỜI CAO TUỔI:
CHỨNG CỨ LIÊN QUAN
ĐẾN THUỐC LỢI TiỂU
PGS TS Trương Quang Bình
ĐHYD TP HCM




Systolic BP:
highly predictive of stroke risk
Stroke mortality*

Age at risk

256

80-89 y

128

70-79 y

64

60-69 y

32

50-59

16
8
4
2
1
0
120
* Floating absolute risk and 95% confidence interval.
SBP, systolic blood pressure.
1. Lewington S et al. Lancet. 2002;360:1903-1913.

140
160
180
Usual systolic BP (mm Hg)
4


Hypertension sub-type According to Age

Franklin SS, et al. Circulation 1997;96: 308-15.


Reflected waves due to stiffer arteries from periphery
increase pulse wave velocity & Systolic BP

1. O’Rourke M. Hypertension. 1995;26:2-9

6

Older patients have a low level of renin activity

Supine plasma renin
activity
(PRA)
and
aldosterone plasma level
as a function of age in
healthy
normotensive
people receiving an ad
libitum sodium diet.

1. Belmin et al. Drugs Aging. 1994;5(5):391-400.

7


Tieán trieån cuûa taêng HA

B. Williams. 2007 Number


Amlodipine has Shown CV Protective Efficacy in
Landmark Studies
PREVENT1
825 CAD patients (≥ 30%); multicentre,
randomized, placebo-controlled

CAMELOT2
1,991 CAD patients (≥ 20%); double-blind,
randomized study vs placebo and enalapril
20 mg

ASCOT-BPLA/CAFE3,4
19,257 HTN patients; multicentre,
randomized, prospective study vs atenolol

ALLHAT5
18,102 HTN patients; multicentre,
randomized, prospective study vs lisinopril

Primary outcome: no difference in mean 3-y coronary
angiographic changes vs placebo
35% ↓hospitalization for heart failure + angina
33% ↓revascularization procedures
Primary outcome: 30%↓in CV events vs placebo
41% ↓hospitalization for angina
27% ↓coronary revascularization

Primary outcome: 10%↓in non-fatal MI and fatal CHD
16% ↓total CV events and procedures
30% ↓new-onset diabetes
27% ↓stroke
11% ↓all-cause mortality
4.3 mmHg ↓central aortic pressure
Primary outcome: no difference in composite of fatal
CHD and non-fatal MI vs lisinopril

6% ↓combined CVD
23% ↓stroke

1. Pitt et al. Circulation. 2000;102:1503–1510; 2. Nissen et al. JAMA. 2004;292:2217–2226; 3. Dahlof et al. Lancet.
2005;366:895–906; 4. Williams et al. Circulation. 2006;113:1213 –1225; 5. Leenen et al. Hypertension.2006;48:374–384.


A = ACE-inh or ARB, C = CCB, D = thiazide type diuretic


11


12

Cumulative Event Rates for All-Cause
Mortality by ALLHAT Treatment Group

ALLHAT
.3

Cumulative Mortality Rate

.25

HR (95% CI)

p value

A/C

0.96 (0.89-1.02)

0.20

L/C

1.00 (0.94-1.08)

0.90

.2

Chlorthalidone
Amlodipine
Lisinopril

.15

.1

.05

0
0
Number at risk:
Chlor
15,255
Amlo
9,048

Lisin
9,054

1

14,933
8,847
8,853

2

14,564
8,654
8,612

3
4
Years to Death
14,077
8,391
8,318

12,480
7,442
7,382

5

6

7

7.185
4,312
4,304

3,523
2,101
2,121

4288
217
144


13

Cumulative Event Rates for Heart Failure
by ALLHAT Treatment Group

ALLHAT

Cumulative CHF Rate

.15

HR (95% CI)

p value

A/C

1.38 (1.25-1.52)

<.001

L/C

1.19 (1.07-1.31)

<.001

.12
Chlorthalidone
Amlodipine
Lisinopril

.09

.06

.03

0
0
Number at risk:
Chlor
15,255
Amlo
9,048

Lisin
9,054

1

2

14,528
8,535
8,496

13,898
8,185
8,096

3
4
Years to HF
13,224
7,801
7,689

11,511
6,785
6,698

5
6,369
3,775
3,789

6
3,016
1,780
1,837

7
384
210
313


HYVET Trial: Study Design
3845 patients > 80 years with continual hypertension and systolic blood pressure ≥
160 mm Hg prior to randomization
Prospective. Randomized. Double Blind. Placebo-Controlled. Mean follow-up 1.8yrs
R

Active Treatment
1.5 mg Indapamide (SR)
n=1933

Placebo
Matching Dose
n=1912
2 yrs. follow-up





Primary Endpoint: fatal and non-fatal strokes
Secondary Endpoints: death from: stroke, cardiovascular
causes, cardiac causes and any cause
N Engl J Med 2008;358/ACC 2008






Thiazide diuretics / CCB combination is recommended
for older hypertensive patients
ESH/ESC guidelines suggest a diuretic or a CCB may be
particularly useful for elderly patients

Mancia G et al. Eur Heart J. 2013;34:2159-2219.

2013
19


Thiazide diuretics / CCB combination is recommended
for older and black hypertensive patients
JNC8 panel report recommends a CCB or a thiazide-type diuretic, alone or in combination for patients over 60

Initiate thiazide –
type diuretic or
CCB, alone or in
combination

James PA et al. JAMA. 2014;311(5):507-520.

2014

20


2015

21


Hypertension Canada CHEP Guidelines
for the Management of Hypertension

2016



Indapamide is more potent than HCTZ & chlorthalidone
at reducing systolic blood pressure
Roush meta-analysis (2015)1

Indapamide is significantly more potent than HCTZ at reducing systolic blood
pressure, which is not the case with chlorthalidone

-9.5
-13.1

-14.6

Systematic review and
meta-analysis; head-tohead RCTs comparing
HCTZ vs indapamide (10
RCTS, n=813) and HCTZ
vs chlorthalidone (3
RCTS, n=70).

-3.6 mm Hg, (NS)

54%
-5.1 mm Hg, (95% CI; -8.7 to -1.6), P=0.004
Roush et al. Hypertension. 2015;65:1041-1046.

24


Indapamide has a better metabolic profile…
Indapamide
Lipid & glucose neutral1

Chlorthalidone
High risk of new onset diabetes2

43%
higher risk

1. Ambrosioni E, Safar M, Degaute JP, et al. J Hypertens. 1998;16:1677-1684; 2. ALLHAT Collaborative Research Group JAMA. 2002;288:2981-2997.

25